tbuckley/cabot-search huggingface dataset:
Abstract 15721: Gender Differences in Temporal Trends and Outcomes of Pulmonary Arterial Hypertension-Related Hospitalizations in the US
Authors: Titilope Olanipekun, Temidayo Abe, Ndausung Udongwo, Valery S Effoe
Journal: Circulation (2022)

Introduction: There is limited data on the gender differences in the trend of hospitalizations related to PAH and associated outcomes in the US Methods: We queried the National Inpatient Sample from 2010 to 2019 to identify PAH admissions using international classification of diseases (ICD) codes 416.0 (ICD-9) and I27.0 (ICD-10) Results: 20,513 hospitalizations with PAH as the primary diagnosis was analyzed during the study period. There were 13,928 women (67.9%) and 6,584 (32.1%) men. The mean age among women (SD) and men (SD) were 66 years (16) and 65 years (17) respectively. Between 2010 and 2019, PAH hospitalization rates declined in both women (13.5% vs. 8.5%], P &lt; 0.001) and men (14.2% vs. 8.3%, P = 0.027. The overall mortality rate was higher in men compared with women (6.6% vs. 5.7%, P = 0.015. Though crude mortality rates declined for the total population, this was statistically significant only among women (6.7% vs.5.6%, P = 0.011). On adjusted multivariate analysis, factors associated with increased odds of inpatient mortality among women were age 45 - 64 years (OR 1.62, 95% CI 1.11 - 2.37, P = 0.013) and &gt; 65 years (OR 2.36, 95% CI 1.57 - 3.55, P&lt;0.001) compared with age 18-44 years. Black (OR 1.44, 95% CI 1. 13 - 1.78, P &lt; 0.001) and Hispanic race/ethnicity (OR 1.06, 95% CI 1.02 - 1.51, P = 0.037), compared with White race/ethnicity. Comorbidities and in-hospital complications associated with increased mortality were chronic kidney disease, acute pulmonary embolism (PE), and acute respiratory failure (ARF). Among men, age &gt; 65 years (OR 3.28, 95% CI 1.68 - 6.41, P = 0.001), Black (OR 1.9, 95% CI 1.36 - 2.91, p &lt; 0.001) and Hispanic race/ethnicity (OR 1.21, 95% CI 1.08 - 1.78, P = 0.021), compared with White race/ethnicity were associated with increased odds of mortality. The presence of congestive heart failure and complications of acute PE, ARF, acute ischemic stroke, and atrial fibrillation were also associated with increased mortality. Conclusions: From 2010 to 2019 in the US, PAH-related hospitalization rates decreased in both women and men while mortality only decreased among women. Men were more likely to die during hospitalization compared with women. Older age and Black and Hispanic race/ethnicity were associated with higher mortality in both women and men.
Abstract 15800: Dissecting Cardiomyocyte-Fibroblast Communication During Homeostasis and Cardiac Fibrosis in a Compartmentalized Biomimetic Tissue Model
Authors: Samuel J DePalma, Darcy Huang, Austin Stis, Brendon M Baker
Journal: Circulation (2022)

Introduction: Cardiac fibroblasts (CFs) maintain cardiac structure and function by synthesizing and remodeling the extracellular matrix (ECM) found throughout the heart. Homeostatic maintenance of the ECM required for healthy tissue function depends on CF communication with cardiomyocytes (CMs). During cardiac fibrosis, signals resulting from tissue injury and dysregulated CF-CM communication promote CF differentiation into α-smooth muscle actin + (αSMA) myofibroblasts (MFs), which deposit excess ECM that mechanically impairs heart function. Given the challenges involved in parsing the dynamic and multifactorial heterocellular interactions underlying tissue homeostasis versus fibrosis, we engineered a compartmentalized, bilayer cardiac tissues where iPSC-derived CMs and CFs can be cultured on either side of a shared fibrous ECM to study CM-CF communication. Methods: Dextran vinyl sulfone (DVS) fibers were electrospun onto arrays of microfabricated PDMS wells. Matrix stiffness and alignment were controlled by modulating the speed of the collecting surface and UV light exposure, respectively. iPSC-CMs and primary human CFs were seeded onto opposing sides of the matrix. Immunostaining for αSMA was conducted to assess CF differentiation to MFs. Results: In CF monocultures on matrices varying in alignment and stiffness, MF differentiation was greatest on stiff (17.3 kPa) aligned matrices with exogenous TGFβ1 compared to soft (0.68 kPa) aligned matrices and both soft/stiff random matrices. We also observed increased nuclear YAP expression on stiff/aligned matrices, indicating altered mechanosensing in response to matrix properties. However, the presence of co-cultured CMs inhibited MF differentiation despite exogenous TGFβ1. MF differentiation was also impaired in CFs cultured on glass below matrix-seeded CMs, implying the role of protective paracrine signaling from CMs to CFs. Conclusions: We developed a microfabricated biomimetic coculture platform to examine CM-CF communication driving tissue homeostasis versus fibrosis. Specifically, we find that fibrous mechanical cues modulate YAP-mediated signaling and αSMA expression. Further, CM-CF paracrine signaling mitigates MF differentiation on aligned fibrous matrices.
Abstract 15523: Breaking Bad - Severe Mechanical Hemolytic Anemia After Failed Mitral Valve Repair
Authors: Akshay Goel, Amanda Lloji, Parija Sharedalal, Matthew W Mcmaster, Neal Shah, Joseph Harburger, Daniel Spevack, Suguru Ohira, Masashi Kai, Howard A Cooper
Journal: Circulation (2022)

Introduction: Hemolytic anemia is a rare complication of mitral valve repair surgery. Mechanisms include a high-velocity regurgitant jet striking the annuloplasty ring or displacement of the annuloplasty ring with para-annular leak. Case Report: A 66 year old man with a past history of coronary artery disease was found to have severe, eccentric mitral regurgitation (MR) due to anterior mitral valve leaflet prolapse/flail at the A2 segment. At another institution, he underwent surgical mitral valve repair involving chordal transfer from P2 to A2 segment, suture closure of the resulting P2 defect, and ring annuloplasty. Intra-operative transesophageal echocardiography confirmed the elimination of MR. Three weeks later the patient presented with fatigue and cola-colored urine. Physical examination revealed a murmur of MR. Lab tests were consistent with severe hemolytic anemia, including hemoglobin of 6 g/dL, indirect hyperbilirubinemia, elevated lactate dehydrogenase, and a low haptoglobin level. Peripheral blood smear showed dysmorphic red blood cells suggestive of mechanical lysis. The patient required multiple transfusions of packed red blood cells. Acute kidney injury developed and was attributed to pigment nephropathy. He was transferred to our institution. Decision-making: Recurrent MR from failure of recent mitral valve repair was suspected. Transthoracic and transesophageal echocardiography confirmed severe eccentric MR. The Heart Team recommended re-operation. In the operating room, the suture repair of the P2 defect was found to have dehisced. Re-repair was deemed infeasible, and the mitral valve was replaced with a porcine bioprosthesis. Post-operatively, hemolysis resolved and renal function recovered. Conclusion: This case illustrates the importance of suspecting hemolysis from recurrent MR in patients presenting with unexplained anemia after mitral valve surgery. Re-operation is generally required to treat this rare condition.
Abstract 213: Remote Ischemic Conditioning To Enhance Resuscitation After Cardiac Arrest
Authors: Emily S Bartlett, Sophie Morse, Lucy Goodson, Dana Morse, Graham Nichol
Journal: Circulation (2022)

Introduction: Restoration of blood flow after out-of-hospital cardiac arrest (OHCA) induces inflammation that causes cellular injury and death. Remote ischemic conditioning (RIC) consists of brief episodes of ischemia then reperfusion to a limb. Trials in animal models in cardiac arrest and in humans with acute infarction show RIC reduces RI. Objective: We sought to demonstrate the feasibility and safety of RIC in patients resuscitated from OHCA and transported to hospital. Methods: Single site 2-arm, single blind randomized feasibility trial comparing a treatment group receiving RIC versus usual care following OHCA. For patients allocated to the intervention group, RIC was performed via 3 cycles of 5-minutes inflation then 5-minutes deflation of a blood pressure cuff applied to an upper extremity. Included were adults resuscitated from OHCA with non-traumatic etiology of arrest, spontaneous circulation present upon emergency department arrival, no response to verbal commands and ongoing or planned induced hypothermia. Excluded were those with: ST-elevation on first 12-lead ECG obtained after return of spontaneous circulation, do not attempt resuscitation (DNAR) status, drowning or hypothermia as cause of arrest, dialysis fistula in either upper extremity or pre-existing amputation of upper extremity, pregnancy or incarcerated status. The primary outcome was attrition, i.e., the proportion of patients enrolled and not on allocated therapy for the study duration. Results: N=30 patients were enrolled (n=14 control, n=16 intervention). Mean age was 52.5 ± 16.2 years. Twenty-seven percent had female gender and 27% had a shockable first recorded rhythm. There was 0% attrition amongst enrolled patients. Other outcomes are summarized (Table). Conclusions: Application of RIC after OHCA is feasible and safe. An adequately powered trial is required to assess whether RIC is effective at decreasing morbidity and mortality after CA. TABLE: OUTCOMES
Abstract 15494: Characterization of Adiponectin Kinetics and Adiponectin R2 Pathway in Thp-1 Macrophages and Foam Cells
Authors: Anouar Hafiane, Jean-Claude Bertrand, Stella S Daskalopoulou
Journal: Circulation (2022)

Background: Adiponectin (APN) is an adipokine most abundantly secreted by adipocytes and possesses vasculoprotective properties. We and others have previously showed that APN receptor 2 (adipoR2) pathway is impaired in foam cells when compared to macrophages. Nevertheless, the functional role of adipoR2 pathway in foam cells has not been fully investigated. We hypothesize that APN kinetics involving AdipoR2 and its subsequent downstream signaling peroxisome proliferator-activated receptor-α (PPAR-α) expression are altered in foam cells when compared to macrophages. Methods: We used THP-1 human macrophage-derived foam cells loaded with oxidized LDL (60μg/ml) and 3H-cholesterol (2μCi/ml) versus control macrophages. APN isomers and PPAR-α protein expression were detected by gradient SDS-PAGE, and Western blotting, respectively. Media cell cultures mixtures were analysed under protease inhibitor by a size-exclusion centrifugal filter molecular weight cut-off 10 kDa. Results: PPAR-α activation significantly increased in APN-treated macrophages (24h) when compared with APN-treated foam cells (24h) with a maximum fold difference of 1.90±1.21, p=0.002 at 10μg APN/mL (PPAR-α: β actin ratio, spectral count; n=10 repeats for each). As a result, in foam cells, APN stimulated PPAR-α with a lower Km molar efficiency (0.06 ± 0.13 μM) and lower velocity Vmax 0.67±0.08 /h-as compared to macrophages (0.023±0.02 μM and 1.37±0.11 /h respectively, p=0.01 for both). In macrophages, APN had smaller dissociation constant Kd (0.037±0.56 μM) than in foam cells (0.10±1.30 μM). APN increased significantly PPAR-α activity rate over time reaching a maximum of 2h, with 1.19±0.02 PPAR-α protein expression in macrophages vs 0.85±0.057 in foam cells. Additionally, the APN dimer/monomer ratio increased over 24h when compared to foam cells, reaching a maximum at 2h in macrophages. Strong correlations were noted between PPARα and APN dimers: in macrophages (r=0.85; p=0.006) and in foam cells (r=0.68, p=0.05). Conclusion: APN stimulates PPARα activity in macrophages, but significantly less in foam cells (weaker kinetic affinity process), suggesting that APN interaction and binding with adipoR2 and subsequent downstream PPARα expression are affected in foam cells.
Abstract 198: Finding The Sweet Spot Of Chest Compression Rate And Fraction For Improved OHCA 72-hour Survival
Authors: Jonathan R Powell, Michelle Nassal, Elisabete Aramendi, Xabier Jaureguibeitia, Erik Alonso, Ahamed H Idris, Ashish R Panchal, Henry Wang
Journal: Circulation (2022)

Introduction: Cardiac arrest resuscitation guidelines recommend optimization of both chest compression rate (CCR) and fraction (CCF). Simultaneous management of CCR and CCF is challenging. The interaction between CCR and CCF is unknown. Our objective was to evaluate the influence of CCR, CCF and their interactions upon OHCA 72-hour survival. Methods: Retrospective analysis of adult OHCA in the Pragmatic Airway Resuscitation Trial (PART). We determined CCF and CCR from automated signal analysis of available CPR process files. CCF categories were &lt;80%, 80-89.99%, and ≥90%. CCR categories were &lt;100, 100-129.99, and ≥130 per minute. The primary outcome was 72-hour survival. We evaluated the multiplicative interaction between CCR and CCF using a) heat maps, and b) linear mixed modeling with EMS agency as a random effect, adjusted for Utstein variables. Results: Of 3,004 enrolled patients, we included 1,606 with available CPR process data. Mean CCR and CCF were 114 compressions/min (SD 9.96) and 88% (SD 0.08). On linear mixed modeling, CCR of &lt;100 (OR 1.55, 95% CI 0.98, 2.44) and ≥130 (OR 1.29, 95% CI 0.86-1.95), referent 100-129.99, was not associated with improved 72-hour survival. A CCF of &lt;80% (OR 1.55, 95% CI 0.98, 2.44) and ≥90% (OR 1.29, 95% CI 0.86-1.95), referent 120-129.99, was also not associated with improved 72-hour survival. Further, the interaction of CCR and CCF was not associated with improved 72-hour survival (p=0.22). Heat map analysis indicated 72-hour survival was lowest when both CCF &lt;80% and CCR &lt;100 per minute, and highest when CCF &gt;90% and CCR &lt;130 per minute (Figure). Conclusion: The interaction between CCR and CCF may influence 72-hour survival. Rescuers must seek to optimize both CCR and CCF during resuscitation attempts. Research in cardiac arrest outcomes should consider this relationship and plan to have sufficient power to explore varying CCR and CCF values when examining OHCA survival.
Abstract 169: End Tidal CO2 In Multimodal Vest CPR
Authors: Norman A Paradis, Ryan Baumgaertner, Luca Neri, Elisha Ronzio, Fink Sarah, Aidan Paradis, Matt T Oberdier, Magda M Ostafe, Karl B Kern, Henry R Halperin
Journal: Circulation (2022)

Introduction: Circumferential constriction vest CPR is more effective at creating forward blood flow than traditional sternal compression only CPR. Active compression-decompression plus the impedance threshold device CPR (ACD-ITD-CPR) incorporates multiple hemodynamic pump mechanisms and also appears more effective. We have developed a new multimodal CPR that combines vest CPR with additional pump mechanisms, one of which is abdominal counterpulsation. Traditional coronary perfusion pressure (CPP) has not been validated during CPR that incorporates compression modalities applied during the relaxation phase. End tidal carbon dioxide (ET-CO2), however, is an indicator of forward blood flow during CPR that is unaffected by relaxation phase compressions. Hypothesis: Multimodal vest CPR that incorporates multiple pump mechanisms may be more effective than standard alternatives as indicated by ET-CO2. Methods: Utilizing a porcine model of ventricular fibrillation, we measured ET-CO2 in: 1) traditional sternal compression CPR (S-CPR), 2) active compression-decompression plus the impedance threshold device CPR (ACD-ITD-CPR) and 3) a new multimodal CPR comprised of circumferential constriction plus abdominal counterpulsation and active sternal decompression (MM-CPR) . After onset of cardiac arrest, 1 min. epochs of each CPR were randomly performed. Results: Seven experiments were performed with a mean number of epochs per experiment of 7. The mean (M + SD) ET-CO2 for S-CPR was 9 + 3 mmHg, for ACD-ITD-CPR 12 + 6, and for MM-CPR 19+8 (P&lt;.05). Conclusions: Multimodal CPR comprising circumferential constriction plus abdominal counterpulsation and active sternal decompression is a promising new type of non-invasive circulatory support.
Abstract 15771: Disparities in Cardiovascular Death Proportions Based on Age-Standardized Gross Domestic Product Classification of Countries: Global Burden of Disease 2019
Authors: Anoop Titus, Mahati Dasari, FNU Avinashsingh Eswarsingh, Abiram Baburaj, Anu Saji, arushi sharma, Pramukh Arun Kumar, Sourbha Dani
Journal: Circulation (2022)

Introduction: Socioeconomic status impact cardiovascular disease outcomes. There is a paucity of data comparing age-standardized Gross Domestic Product (aGDP) and age-based proportion of CVD deaths (pCVD). Methods: We analyzed World Development Indicators and Global Burden of Disease 2019 study data. aGDP, CVD, total all-cause deaths, and their distribution amongst ‘High Income’ (HI), ‘Upper-Middle Income’ (UM), ‘Low-Middle Income’ (LM), and ‘Low Income’ (LI) countries from 2010-2019 was queried. ANOVA with Kruskal-Wallis Test followed by post-hoc analysis with Tukey test was conducted to examine the differences in pCVD among different income category countries based on age groups (Table 1b). Results: A total of 169,825,716 CVD (35.4%) were noted out of 478,797,297 total all-cause deaths globally. There was a significant difference comparing all income classes (p &lt; 0.001) in age groups except between UM and LI in the age groups 15-49 and 50-69 (p = 0.885 and 0.261 respectively). In the age group 5-14, pCVD was higher in HI, UM, LM and LI classes (3.74%, 3.41%, 2.48 and 1.96%, p &lt; 0.01). In age groups 15-49, pCVD was higher in UM and LM (17.70%, 17.50%), and lower pCVD in HI and LI classes (15.07% and 8.52%). At the age &gt; 70, higher pCVD was seen in UM, followed by LM, LI, and HI (50.05%, 40.93%, 36.74% and 35.78% respectively, p &lt; 0.001). The highest overall pCVD was observed in the UM class. Conclusions: Our study shows a statistically significant difference in pCVD between the World Bank classes of countries based on age groups. There is higher pCVD in HI, both-middle-income, and UM classes in the age groups 5-14,15-69, and &gt;70 respectively, with overall pCVD being higher in UM class.
Abstract 15637: Detection and Characterization of Fibrin/Amyloid Microclots in Patients With Post-Acute Sequelae of Covid-19
Authors: Melanie Walker, Emma M Federico, Douglas B Kell, Christopher Dupont, Amy Proal, Etheresia Pretorius
Journal: Circulation (2022)

LongCovid or Post-Acute Sequelae of COVID-19 (PASC) is a diagnosis given to patients who experience a wide range of debilitating chronic symptoms after infection with SARS-CoV-2. The majority of individuals are PCR negative, indicating microbiological recovery. There are currently few LongCovid/PASC blood-based biomarkers. We used fluorescence microcopy to identify unique fibrin/amyloid micro-thrombosis and hyperactivated platelets in individuals with PASC. These fibrin/amyloid microclots may impede blood flow to tissue. Methods: Whole blood was collected in citrate tubes from 30 matched healthy subjects and 30 PASC subjects. Platelet poor plasma (PPP) was prepared by centrifugation and stored at -80 °C. PPP was then exposed to thioflavin T (ThT), a fluorescence marker known to bind to and open hydrophobic areas on damaged amyloidogenic protein. Samples were viewed with fluorescence microscopy using a 63x/1.4 Oil DIC M27 objective (excitation wavelength 450nm-488nm, emission 499nm- 529nm). After a double-trypsin PPP digestion method, proteomic analysis of the PPP samples was performed. Results: Significant microclot load was observed in the PPP of participants with PASC compared to healthy participants (Fig. 1). Proteomic analysis revealed the presence of inflammatory molecules within digested microclots. Conclusion: Preliminary results suggest that the presence of microclots in PPP may be used as a diagnostic biomarker for the PASC. Characterization of inflammatory molecules and antibodies trapped within microclots might provide insight into the pathogenesis of PASC and serve as a basis for novel treatment strategies or preventative medicine. Figure: Representative specimens A) Microclots in healthy plasma. B) Microclots in PASC plasma.
Abstract 15872: Association Between Cognition and Cardiovascular Function is Modified by Carnosine and Carnosine-Acrolein Conjugates
Authors: Alok R Amraotkar, David Hoetker, Megh S Kumar, Jingjing Zhao, Daniel Gomes, Aruni Bhatnagar, Mathias Basner, Timothy O'Toole
Journal: Circulation (2022)

Background: Carnosine, a naturally occurring dipeptide found in highly metabolic tissues like skeletal muscles and brain can reduce oxidative stress caused by acrolein and particulate matter (PM) exposure. The role of carnosine and its acrolein-conjugates (propanol and propanal) maybe crucial in reducing the effects of PM2.5 air pollution on cardiovascular (CV) health. Methods: We analyzed data of 103 healthy participants from baseline (Visit # 2, before randomization) of the ongoing Nucleophilic Defense against Particulate Matter Toxicity (NEAT) clinical trial (NCT03314987) which investigates whether dietary supplementation of carnosine can protect against effects of PM2.5 air pollution. All participants underwent computerized cognitive test “Cognition”. The Cognition test includes 10 neurocognitive test batteries (Table 1) and assesses distinct domains of cognition. Tests scores were assessed in blinded fashion by the University of Pennsylvania team for individual batteries and a cumulative score. Two-tailed Spearman’s rho was used for correlation and Generalized Linear Models (GLM) with gamma distribution log-link was used for regression. Results: Cumulative cognition score showed a negative association with pulse pressure. Carnosine-propanol levels had a significant modifying effect (Figure 1). Stratified analysis showed that this relationship was significantly modified by low (B= -0.03, P=0.005) and medium (B= -0.016, P=0.046) carnosine-propanol levels. High levels of carnosine-propanol or carnosine-propanal did not show any effect on the cognition-pulse pressure. Indices of metabolic syndrome were also negatively associated with cumulative score (all P&lt;0.05). Conclusions: Carnosine readily reacts with acrolein to reduce in-vivo oxidative stress by producing propanol and propanal aldehyde conjugates. Decrease in propanol conjugates is associated with higher CV health and in-turn higher cognitive outcomes.